AB0068 LOW-DOSE RADIOTHERAPY ATTENUATES EXPERIMENTAL AUTOIMMUNE ARTHRITIS BY INDUCING LYMPHOCYTE APOPTOSIS
Authors: Y. H. Cheon, B. G. Kim, H. S. Choi, Y. Choe, H. M. Jeon, J. Y. Heo, S. I. Lee, B. K. Jeong, M. Kim
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Disease-Modifying Anti-Rheumatic Drugs (DMARDs) have therapeutic effects on rheumatoid arthritis (RA) through the modulating immune responses of systemic and synoviums. However, DMARDs be used for an extended period, drug-related adverse effects can be a severe problem. Therefore, it is necessary to develop a treatment strategy to minimize the adverse effects of DMARDs, such as infection, abnormal liver function tests, and hematological abnormalities. <h3>Objectives</h3> Radiation therapy is one of the crucial therapeutic strategies for cancers. Low-Dose Radiotherapy (LDRT), the total dose may be given in fewer treatments or over a shorter period, has been tried to treat various inflammatory diseases, but its theoretical basis is poor. Therefore, this research aims to elucidate the mechanism and standardization of LDRT for RA. <h3>Methods</h3> The CIA (collagen-induced arthritis) and K/BxN mice used an experimental arthritic model representing RA. At the point of the highest arthritis symptoms, CIA and K/BxN mice were treated with LDRT. Then, the clinical score of the fore or hind paws was measured twice a week for 30 days. After 30 days of LDRT, the mice were sacrificed. Splenocytes, popliteal and inguinal lymphoid cells were analyzed by flow cytometry to measure the level of activation, proliferation, inflammatory-cytokines, and apoptosis of immune cells. To evaluate whether LDRT is effective on human immune cells, RA patients' PBMC were treated with LDRT and analyzed by flow cytometry. <h3>Results</h3> LDRT did not affect the lymphocyte activation, proliferation, differentiation, and inflammatory cytokine secretion. However, LDRT enhanced lymphocyte apoptosis and decreased immune cell numbers and clinical scores in CIA and K/BxN mice. In addition, the degree of cartilage destruction was reduced by treating with LDRT in K/BxN mice. Likewise, the proportion of apoptotic lymphocytes was increased by LDRT in PBMC of a patient with RA, not fibroblast-like synoviocytes (FLS). <h3>Conclusion</h3> We uncovered that LDRT diminished experimental arthritis such as CIA and K/Bx models via augmented lymphocyte apoptosis in draining lymph nodes. Thus, these findings suggest that LDRT can be a new therapeutic strategy with minimal adverse effects for RA. <h3>References</h3> [1]Giaj-Levra N, Sciascia S, Fiorentino A, Fersino S, Mazzola R, Ricchetti F, Roccatello D, Alongi F. Radiotherapy in patients with connective tissue diseases. Lancet Oncol. 2016 Mar;17(3):e109-e117. doi: 10.1016/S1470-2045(15)00417-9. Epub 2016 Mar 2. PMID: 26972857. [2]Mahler EAM, Minten MJ, Leseman-Hoogenboom MM, Poortmans PMP, Leer JWH, Boks SS, van den Hoogen FHJ, den Broeder AA, van den Ende CHM. Effectiveness of low-dose radiation therapy on symptoms in patients with knee osteoarthritis: a randomised, double-blinded, sham-controlled trial. Ann Rheum Dis. 2019 Jan;78(1):83-90. doi: 10.1136/annrheumdis-2018-214104. Epub 2018 Oct 26. PMID: 30366945. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.